Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices

Green, Victoria L.; Greenman, John; Carr, Simon D.; Stafford, Nicholas D.

Abstract

Objective The aim of this study was to investigate how head and neck squamous cell carcinoma (HNSCC) tissue biopsies maintained in a pseudo in vivo environment within a bespoke microfluidic device respond to radiation treatment. Study Design Feasibility study. Setting Tertiary referral center. Subjects and Methods Thirty-five patients with HNSCC were recruited, and liver tissue from 5 Wistar rats was obtained. A microfluidic device was used to maintain the tissue biopsy samples in a viable state. Rat liver was used to optimize the methodology. HNSCC was obtained from patients with T1-T3 laryngeal or oropharyngeal SCC; N1-N2 metastatic cervical lymph nodes were also obtained. Irradiation consisted of single doses of between 2 Gy and 40 Gy and a fractionated course of 5×2 Gy. Cell death was assessed in the tissue effluent using the soluble markers lactate dehydrogenase (LDH) and cytochrome c and in the tissue by immunohistochemical detection of cleaved cytokeratin18 (M30 antibody). Results A significant surge in LDH release was demonstrated in the rat liver after a single dose of 20 Gy; in HNSCC, it was seen after 40 Gy compared with the control. There was no significant difference in cytochrome c release after 5 Gy or 10 Gy. M30 demonstrated a dose-dependent increase in apoptotic index for a given increase in single-dose radiotherapy. There was a significant increase in apoptotic index between 1×2 Gy and 5×2 Gy. Conclusion M30 is a superior method compared with soluble markers in detecting low-dose radiation-induced cell death. This microfluidic technique can be used to assess radiation-induced cell death in HNSCC and therefore has the potential to be used to predict radiation response.

Citation

Green, V. L., Greenman, J., Carr, S. D., & Stafford, N. D. (2014). Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices. Otolaryngology and head and neck surgery, 150(1), 73-80. https://doi.org/10.1177/0194599813507427

• Acceptance Date: Jan 1, 2013
• Online Publication Date: Oct 4, 2013
• Publication Date: 2014-01
• Deposit Date: Dec 22, 2015
• Publicly Available Date: Nov 23, 2017
• Journal: Otolaryngology - head and neck surgery
• Print ISSN: 0194-5998
• Electronic ISSN: 1097-6817
• Publisher: SAGE Publications
• Peer Reviewed: Peer Reviewed
• Volume: 150
• Issue: 1
• Pages: 73-80
• DOI: https://doi.org/10.1177/0194599813507427
• Keywords: Microfluidic techniques, Radiotherapy, Head and neck squamous cell carcinoma, Rat liver
• Public URL: https://hull-repository.worktribe.com/output/383409
• Publisher URL: http://oto.sagepub.com/content/150/1/73
• Additional Information: Copy of article first published in: Otolaryngology - head and neck surgery, 2014, v.150, issue 1.